Placebo-controlled, proof-of-concept oral dose study to explore the safety, pharmacokinetics and pharmacodynamics in subjects with mild to moderate ulcerative colitis

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2012-005521-73-BE
• Date of registration: 08/02/2013
• Prospective Registration: Yes
• Primary sponsor: Galapagos NV
• Public title: Placebo-controlled, proof-of-concept oral dose study to explore the safety, pharmacokinetics and pharmacodynamics in subjects with mild to moderate ulcerative colitis
• Scientific title: Exploratory, Phase II, Randomized, Double-blind, Placebo-controlled, Proof-of-Concept study to evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of GLPG0974 in subjects with mild to moderate Ulcerative Colitis - Proof-of-concept oral dose, safety, tolerability, efficacy, PK and PD study
• Date of first enrolment: 20/03/2013
• Target sample size: 45
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-005521-73
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Exploratory, proof-of-concept If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Czech Republic, Latvia

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Galapagos NV

• Name: Clinical Trial Information Desk
• Affiliation: Galapagos NV

Key inclusion & exclusion criteria

Inclusion criteria:
1.Men or women between 18 to 75 years of age inclusive, on the day of signing the informed consent.
2.Documented history of UC (at least 6 months prior to randomization) with histological confirmation of diagnosis.
3.Presence of mild-to-moderately active ulcerative colitis for a minimum period of 14 days and spread beyond the rectum (inflammation extending =15 cm from anal verge) as evidenced by clinical signs and endoscopy.
4.Medication: 5-ASA for at least 12 weeks and stable dose for > 4 weeks or discontinued for> 4 weeks prior to randomization. Rectal medications stopped for > 2 weeks prior to randomization.
5.Baseline Mayo score 4-10 (inclusive) with rectal bleeding sub-score of = 1, endoscopy score = 1 and Physician’s rating of disease activity < 3.
6.Absence of infectious colitis as evidenced by negative stool culture for enteric pathogens, negative Clostridium difficile cytotoxin assay, and negative microscopic stool examination for intestinal parasites.
7.Women must have a negative pregnancy test unless they are surgically sterile or have been post-menopausal for at least one year (12 consecutive months without menses); in case of doubt a determination of serum follicle stimulating hormone (FSH) can be done with FSH levels above 35 mIU/mL being confirmative for menopause.
8.Women of childbearing potential must use a medically acceptable form of birth control and agree to continue its use during the study and for at least twelve weeks after the last dose of study drug. Women who have had a complete surgical hysterectomy or are postmenopausal are exempt from this requirement. Medically acceptable forms of birth control include oral contraceptives, injectable or implantable methods, intrauterine devices, tubal ligation (if performed more than one year before screening), or double barrier contraception. Sexually active men must agree to use a medically acceptable form of contraception (double barrier) during the study and continue its use for at least twelve weeks after the last dose of study drug.
9.Able and willing to give voluntary written informed consent and agree to schedule of assessments.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1.History of sensitivity to any component of the study drug, or a history of drug or other allergy that, in the Investigator’s opinion, contraindicates subject’s participation in the study.
2.Any concurrent illness, condition, disability or clinically significant abnormality (including laboratory tests) that, in the Investigator’s opinion, represents a safety risk for subject’s participation in the study, may affect the interpretation of clinical safety or efficacy data, or may prevent the subject to safely complete the assessments required by the protocol, including:
a.Hemoglobin <8.5 g/dL
b.White blood cells (WBC) count <3.0 x 109 cells/L
c.Neutrophil count <1.5 x 109 cells/L
d.Platelet count <100 x109 cells/L
e.Serum ALT >1.5 x upper limit of normal (ULN)
f.HbA1c > 6%
g.Total bilirubin level >1.25 x ULN
h.Creatinine clearance <80 mL/min using the Cockroft-Gault formula
3.Positive serology for human immunodeficiency virus (HIV)1 or 2 or hepatitis B or C, or any history of HIV or hepatitis from any cause with the exception of hepatitis A.
4.History of active infections requiring intravenous antibiotics within the past four weeks prior to randomization.
5.History of malignancy within the past five years (except for basal cell carcinoma of the skin or carcinoma in situ of the cervix that has been treated with no evidence of recurrence).
6.History of bowel surgery within 12 months prior to screening, or presence or history of intestinal malignancy (if any unexpected lesion is observed during screening endoscopy, additional biopsies should be taken for histopathological assessment in the local lab to and recruitment into the study must be deferred until the results are available).
7.Suspicion of Crohn’s disease, indeterminate colitis, microscopic colitis, ischaemic colitis or radiation-induced colitis, based on medical history, endoscopy and/or histological findings. For subjects with a documented history of UC of = 8 years a total colonoscopy should have been done within the 2 years prior to screening or performed at Day 1 prior to randomization. to exclude the aforementioned conditions.
8.History of lower GI bleeding disorder, other than UC.
9.A history of significant psychological, neurologic, hepatic, renal, endocrine, cardiovascular, gastrointestinal (other than UC), pulmonary or metabolic disease.
10.History of tuberculosis (TB) infection as determined by:
a.positive diagnostic TB test result (defined as a positive QuantiFERON
TB Gold test),
OR
b.a chest radiograph (both posterior-anterior and lateral views), taken within
three months prior to screening and read by a qualified radiologist, with
evidence of current active TB or old inactive TB.
i.e. both tests must be negative for thesubject to be eligible.
11.Treatment with systemic corticosteroids within 1 week prior to randomization.
12.If topical corticosteroids are being used for other chronic inflammatory conditions, the subject may be included at the discretion of the Investigator after discussion with the medical monitor.
13.Treatment with TNF-a inhibitors or other biologics within 2 months prior to randomization.
14.Treatment with immunosuppressants (azathioprine or 6-mercaptopurine or methotrexate), if initiated within 3 months prior to randomization, or if changed in terms of drug or dose within 3 months prior to randomization .
15.Current use of probiotic or

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Mild to moderate Ulcerative Colitis
MedDRA version: 16.0 Level: PT Classification code 10009900 Term: Colitis ulcerative System Organ Class: 10017947 - Gastrointestinal disorders

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: GLPG0974
Pharmaceutical Form: Capsule
INN or Proposed INN: GLPG0974
Current Sponsor code: G279874
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Safety Endpoints:
- Frequency of Serious adverse events in GLPG0974 versus placebo group.
- Frequency of Adverse events in GLPG0974 versus placebo group.
- Changes in physical examinations, vital signs, 12-lead ECG and laboratory parameters over the duration of the study in GLPG0974 versus placebo group.

Secondary Objective: 1.To explore the efficacy of GLPG0974 versus placebo in mild to moderate Ulcerative Colitis (UC) by use of efficacy measures such as the Mayo score, Partial Mayo Score and histopathological Geboes index
2.To characterize the PK of GLPG0974 in UC subjects.
3.To explore the effects of GLPG0974 on selected biomarkers (e.g. faecal calprotectin, MPO in biopsy and serum CRP) and on microbiota.

Main Objective: To evaluate the safety and tolerability of GLPG0974 given to UC subjects for 28 days compared to placebo.

Timepoint(s) of evaluation of this end point: At different timepoints from signing informed consent until follow-up visit : (S)AE, laboratory parameters
Scr., D1, D8, D29 and D43: ECG and Vital signs
Scr., D1, D29 and D43: Physical exam

Secondary Outcome(s)

Secondary end point(s): Efficacy Endpoints:
- Mayo score
- Partial Mayo Score
- Geboes Index

PK parameters:
- GLPG0974 in blood
PD parameters:
- fecal calprotectin analysis on stool samples
- MPO measurement on biopsy samples
- serum CRP analysis
- microbiota analysis on stool and biopsy samples

Timepoint(s) of evaluation of this end point: Efficacy Endpoints:
- Mayo score: D1 and D29
- Partial Mayo score: D8 and D15
- Geboes Index: D1 and D29

PK parameters: D8, D15 and D29

PD parameters:
- fecal calprotectin analysis on stool samples: D1, D8, D15 and D29
- MPO measurement on biopsy samples: D1 and D29
- serum CRP analysis: Scr., D1, D8, D15, D29 and D43
- microbiota analysis on stool and biopsy samples D1 and D29

Secondary ID(s)

GLPG0974-CL-201

Source(s) of Monetary Support

Galapagos NV